Although we all know one or more individuals who can't sing in tune, the neural correlates of this disorder and what it might reveal about models of communication control remain elusive. In addition to an inability to sing in tune, one characteristic marker of tone-deafness is an abnormally large psychophysical pitch discrimination threshold of more than one semitone. The inability to discriminate fine pitch differences may be an epiphenomenon of the disorder, or it could be related to the presumed auditory-motor dysfunction that underlies disabled production of vocal pitch. Pilot and previous data from morphometric, functional imaging, and Event- Related Potential (ERP) studies point towards functional and structural abnormalities in regions involved in auditory feedback control and sound-motor mapping, rather than dysfunctions in primary auditory cortex. In considering that the inability to sing might be reflective of problems in auditory-motor integration including feedforward and feedback control mechanisms, the present theoretical framework allows us to generalize existing models of speech perception and production to the domain of singing as an instance of "intoned-speech". Our general hypothesis is that tone-deafness is a result of dysfunction in a network of brain regions involved in auditory feedback and feedforward control of vocal pitch production. We plan to test this hypothesis by first identifying the behavioral and neural substrates of tone-deafness. By combining neuroimaging and psychophysical experiments of pitch production, including the use of pitch- shifted auditory feedback, we will test the neural mechanisms responsible for auditory feedback control and sound-motor mapping as well as the interaction of these two systems (Aim 1). We will then reverse-engineer the perceptuomotor pathway by creating temporary regional dysfunctions using a new method of non-invasive brain stimulation (transcranial direct current stimulation - TDCS) (Aim 2). Based on pilot pitch production results, brain stimulation can temporarily induce tone-deafness in normal individuals, thus allowing us to assess our regional hypotheses using psychophysical measures that have been evaluated in experiments from the first aim. Examining the neural correlates of tone-deafness and creating a tone-deaf equivalent in normal subjects will offer new insights into the interactions of auditory and motor systems in the brain in normal and disordered speech as well as in non-speech communication. PUBLIC HEALTH RELEVANCE People who are tone-deaf typically cannot sing in tune, suggesting impairments in brain regions controlling auditory and motor systems. By combining brain imaging with singing tests in tone-deaf and normal individuals, and simulating abnormal singing via non-invasive brain stimulation, the proposed research will identify and test the neural substrates of tone-deafness.